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1,1,1,2-Tetrafluoroethane is an inert gas used primarily as a "high-temperature" refrigerant for domestic refrigeration and automobile air conditioners. These devices began using 1,1,1,2-tetrafluoroethane in the early 1990s as a replacement for the more environmentally harmful R-12 and retrofit kits are available to convert units that were originally R-12-equipped. Other uses include plastic foam blowing, as a cleaning solvent, a propellant for the delivery of pharmaceuticals (e.g. bronchodilators), wine cork removers, gas dusters and in air driers for removing the moisture from compressed air. 1,1,1,2-Tetrafluoroethane has also been used to cool computers in some overclocking attempts. It is also commonly used as a propellant for airsoft airguns.

Tetrafluoroethane, when compressed as inside gas duster cans, is a clear liquid which boils when exposed to atmospheric pressure at room temperature (as seen here) and can be extracted from common "canned air" canisters by simply inverting them during use.

1,1,1,2-tetrafluoroethane is also being considered as an alternative to sulfur hexafluoride as a dielectric gas.[10] Its arc-quenching properties are poor, but its dielectric properties are fairly good.

An additional use of 1,1,1,2-tetrafluroethane is as a propellant. It is used in this way mainly for gas-powered airsoft guns. The gas is often mixed with a silicon-based lubricant.

The Society of Automotive Engineers (SAE) has proposed 1,1,1,2-tetrafluoroethane (HFC-134a) to be best replaced by a new fluorochemical refrigerant HFO-1234yf (CF3CF=CH2) in automobile air-conditioning systems.[12] California may also prohibit the sale of canned 1,1,1,2-tetrafluoroethane to individuals to avoid non-professional recharge of air conditioners.[13] A ban has been in place in Wisconsin since October 1994 under ATCP 136 prohibiting sales of container sizes holding less than 15 lbs of 1,1,1,2-tetrafluoroethane, but this restriction applies only when the chemical is intended to be a refrigerant. The ban has been lifted in Wisconsin in 2012.[14] It appears, for example, that it is legal for a person to purchase gas duster containers with any amount of the chemical because in that instance the chemical is neither intended to be a refrigerant [14] nor is HFC-134a included in the § 7671a listing of class I and class II substances.[15]

1,1,1,2-Tetrafluoroethane first appeared in the early 1990s as a replacement for dichlorodifluoromethane (R-12), which has ozone depleting properties.[16] 1,1,1,2-Tetrafluoroethane has been atmospherically modeled for its impact on depleting ozone and as a contributor to global warming. Research suggests that over the past 10 years the concentration of 1,1,1,2-tetrafluoroethane has increased significantly in the Earth's atmosphere, with a recent study revealing a doubling in atmospheric concentration between 2001 and 2004.[17] It has insignificant ozone depletion potential (ozone layer), significant global warming potential (100-yr GWP = 1430)[18] and negligible acidification potential (acid rain). Because of its high GWP, 1,1,1,2-tetrafluoroethane has been banned from use in the European Union, starting with cars in 2011 and phasing out completely by 2017.[19]

Contact of 1,1,1,2-tetrafluoroethane with flames or hot surfaces in excess of 250 °C (482 °F) may cause vapor decomposition and the emission of toxic gases including hydrogen fluoride and carbonyl halides.[20] 1,1,1,2-Tetrafluoroethane itself has an LD50 of 1,500 g/m3 in rats, making it relatively non-toxic, apart from the dangers inherent to inhalant abuse. Its gaseous form is denser than air and will displace air in the lungs. This can result in asphyxiation if excessively inhaled.[21][22] This is what contributes to most deaths by inhalant abuse.

Aerosol cans containing 1,1,1,2-tetrafluoroethane, when inverted, become effective freeze sprays. Under pressure, 1,1,1,2-tetrafluoroethane is compressed into a liquid, which upon vaporization absorbs a significant amount of thermal energy. As a result, it will greatly lower the temperature of any object it contacts as it evaporates. This can result in frostbite when it contacts skin, as well as blindness upon eye contact.